While eating a hamburger at a neighborhood restaurant, University of Pittsburgh alumnus Paul Lauterbur scribbled some thoughts on a paper napkin. What he wrote changed health care forever. It also led, more than three decades later, to a telephone call from Stockholm.

Magnetic Personality

Darkness covers the flat farmlands of east-central Illinois on this autumn morning. The birds aren’t yet awake, and the sun won’t peep above the horizon for hours. The sidewalks along Urbana-Champaign’s lush campus quads are bathed in pools of soft lamplight, empty except for the occasional brown rabbit crossing to forage in nearby shrubs. A few miles away in a home on Holcomb Drive, two people are sound asleep in the bedroom.

Suddenly, Paul Lauterbur feels the poking. It’s 3:30 a.m., and Joan Dawson gently prods her husband awake. He emerges from a deep slumber. He didn’t hear the phone ringing. As soon as his eyes flicker awake, his wife says: “It’s Stockholm calling.” A day that begins in utter quiet soon changes.

Lauterbur (FAS ’62) was born a chemist. At least, he says, his interest in chemistry is akin to breathing. It just comes naturally. He loved, for instance, his boyhood chemistry sets. The typical set of that era came in a wooden, hinged box that opened to reveal an exotic world. There were envelopes marked No. 11 Zinc, No. 18 Blue Litmus Indicator, No. 32 Congo Red Indicator, No. 58 Flame Test Wire, and other mysterious labels. There were glass vials tucked into a removable plywood tray, with corks to top the vials. Chunky bottles rested on built-in shelves, along with assorted spoons, stirrers, and powders.

When Lauterbur was barely a teenager, he went beyond store-bought chemical kits to create a basement laboratory in his family’s home in Sidney, Ohio. He bought glassware with his allowance and experimented with new chemical concoctions. “Kids always like to do things that are a little bit out of the ordinary, especially if they make a loud noise,” he says. “I don’t think that’s so unusual.”

But there was something uncommon about Lauterbur. Throughout his youth, chemical puzzles kept their allure, and he kept learning. At Sidney High School, the chemistry teacher often let him work on his own, well ahead of most classmates. Already, the quiet, studious teenager showed traits that would lead, one day, to that phone call from Stockholm.

“I woke up reasonably quickly,” recalls Lauterbur, who is a professor at the University of Illinois, Urbana-Champaign. The call was from a member of the Karolinska Institutet, an esteemed Swedish institute for medical education and research. The news was good, really good. In two hours, the institute would announce to the world that Lauterbur had won the 2003 Nobel Prize in Physiology or Medicine, perhaps the most coveted and celebrated honor on the planet. Lauterbur would share the prize and its $1.3 million award with Sir Peter Mansfield at the University of Nottingham, England.

Alfred Nobela Swedish chemist, engineer, and inventorestablished Nobel Prizes in his will to honor “those who ... have conferred the greatest benefit to mankind.” The prizes, first presented in 1901, bring worldwide recognition. They are now given in six categories: physics, chemistry, physiology or medicine, literature, economics, and peace. Across categories, past Nobel laureates include Madame Curie, Albert Einstein, Ernest Hemingway, and Martin Luther King Jr.

By the time the sun rose, Lauterbur’s phone barely stopped ringing. Family called. Colleagues called. Friends called. Friends of friends called. There were requests for visits, speaking engagements, and honorary fetes. NPR’s Morning Edition wanted an interview. So did The New York Times, The Washington Post, USA Today, the Chicago Tribune, and others. “Nobel madness,” says Lauterbur.

The work that earned him the Nobel Prize has saved millions of lives and changed the course of medical practice.

He didn’t start out with such high aspirations. After graduating in 1951 with a BS in chemistry from Cleveland’s Case Institute of Technology (now Case Western Reserve University), Lauterbur began working at Pittsburgh’s Mellon Institute of Industrial Research. In those days, many corporations didn’t have their own research facilities. Instead, they formed partnerships with independent research institutes. The Dow Corning Co. recruited Lauterbur to conduct research at the institute, where the environment was far more academic than corporate. This was, in part, because the University of Pittsburgh was informally affiliated with the institute. Lauterbur took advantage of the setting, including its educational benefits. “I was living in a boarding house up on North Dithridge Street but spending most of my time at Mellon Institute and climbing up the hill to Pitt’s chemistry department, where I took many, many courses,” he recalls.

Soon after his arrival, he attended a Mellon Institute seminar that introduced him to a new research tool. The technology was based on discoveries by physicists about a phenomenon they called nuclear magnetic resonance, or NMR. “I was very interested in how molecules are put together, and it looked like a much clearer way of solving chemistry problems than anything else I had heard of at that time,” says Lauterbur. He wanted to know more.

NMR works because atoms have magnetic qualities. Atoms are the building blocks of all matter, far tinier than pin tips. They consist of even smaller particlesprotons, neutrons, and electrons, which carry electrical charges. The protons and neutrons form an atom’s core, or nucleus, while electrons orbit nearby. These particles spin, like miniplanets, creating magnetic forces within the atom. In the 1940s, physicists discovered they could manipulate these magnetic properties, using external magnets. When placed in a strong magnetic field from an external sourcesay, a researcher’s labthe nuclei of certain atoms spin at a frequency determined by the strength of that field. If researchers then apply radio waves at the same frequency, the nuclei absorb additional energy from those waves. When the external magnet is turned off, the nuclei “relax,” returning to their original energy level. In the process, they expel the excess energy as radio wave signals, which can be detected and analyzed. Researchers use this information to understand atomic structures.

Lauterbur was intrigued by this discovery, which won the Nobel Prize in Physics in 1952. He was among the first cluster of chemists to use NMR in studies of chemical molecules, solutions, and solids. His tutelage in the field began in an unexpected place. In 1955, the draft board plucked him from Pittsburgh. Within months, he was assigned to the medical laboratories at the Army Chemical Center in Edgewood, Md. Chatting with another soldier, he learned that an NMR machine would soon arrive. “I could actually pronounce ‘nuclear magnetic resonance,’ so I became the base expert,” says Lauterbur, only half joking. He helped set up the new lab, and the remainder of his army duty was spent living with that NMR machine.

This experimental equipment cost the equivalent of $10 million or more in today’s dollars. Lauterbur was among a small cadre of researchers who had access, gaining expertise relatively few others could claim. When he completed his army service, he returned to Mellon Institute, no longer just a traditional chemist. He convinced his research administrators to invest in an NMR machine. He also continued to climb up the hill to Eberly Hall, receiving his PhD in chemistry from Pitt in 1962.

His doctoral thesis focused on carbon-13, an isotope of ordinary carbon, the basis for all organic compounds. He then used carbon-13 NMR to determine the chemical molecular structures of many compounds.

Over the next decade, he continued to gain expertise in the novel NMR technology. While working as an NMR-immersed chemist, Lauterbur and a colleague even started a firm called NMR Specialties that sold NMR equipment to institutions and corporations. The technology had increasingly gained respect not only among physicists but also chemists and medical researchers who were interested in the body’s chemistry.

When Lauterbur left Pittsburgh in 1963 to join the chemistry faculty of the State University of New York (SUNY) at Stony Brook, he maintained an informal consulting role with NMR Specialties, located in a warehouse just north of Pittsburgh. As part of its sales strategy, the company made its equipment available to potential customers.

Lauterbur happened to be on site when a potential customer showed up just before the Labor Day weekend in 1971. Leon Saryan, a researcher from Johns Hopkins University School of Medicine, placed healthy tissue in a test tube while Lauterbur watched. The tissue had just been cut from a lab rat. Saryan wanted to see if he could confirm published research findings, which suggested that NMR could distinguish the chemical composition of normal tissue from cancerous tissue.

Saryan positioned the test tube in the NMR machine, surrounding the tissue with external magnets. A pen-stylus recorded the readings from the machine’s signals on graph paper, much like the output of a polygraph machine. When that process ended, Saryan then placed another test tube, containing cancerous rat tissue, in the machine. The process was repeated on this sample and other tissue samples during the day.

‘Nobel madness,’ says Paul Lauterbur, a professor at the University of Illinois, Urbana-Champaign, of the reaction generated when he and Sir Peter Mansfield won a Nobel Prize in Medicine for the work on magnetic resonance imaging. (Photo by Bill Wiegand. University of Illinois at Urbana-Champaign photo, used with permission.)

Lauterbur was curious about the way different types of tissues from rats produced different NMR signals. Cancerous tissue appeared to be different from normal tissue, but normal tissue also varied in signal from sample to sample.

While the testing confirmed that NMR could differentiate tissue, there were some significant limitations. The biggest was the magnet’s lack of uniformity. A uniform magnetic field gives the clearest, sharpest signal. But no magnet produces a totally uniform magnetic field. Some spots in the magnet produce a weaker field than other spots, and this can distort the signal reading, in effect “blurring” the radio signals and making them difficult to interpret.

Also, to prevent the radio frequency signals from being distorted beyond interpretation, the size of an object couldn’t be much bigger than a cigar.

During the Saryan experiments, Lauterbur thought about these limitations and the technology’s practicality when he took a dinner break with Don Vickers, a friend and company officer. Lauterbur recalls that “on the second bite of a Big Boy hamburger,” he was struck by an idea. Maybe that “blurring” contained embedded information that he could decipher. Vickers remembers him saying: “Heck, you could make pictures with this thing!”

Quickly, Lauterbur left the restaurant with his napkin notes to buy a notebook at a local drugstore. He spent much of that night refining his thoughts. “I had to convince myself that I was not just on a wild-goose chase,” he says. Before he fell asleep, he had crystallized his concept and neatly written his proposed theory on several sheets of notebook paper.

Lauterbur’s Big Boy revelation was to find a way to break down the whole signal field into smaller quadrants. These sections would reveal more specific details about the larger field. Then, by applying a gradient magnetic field across the broader primary field, he believed he could extract more detailed information about what was going on within these more defined spaces of the signalnot only left-to-right, but also top-to-bottom and front-to-back. These information-rich spaces might then be assembled collectively to provide, for the first time, an image of the complete objecta cross-sectional picture instead of a flat series of dots and lines.

When Lauterbur returned to SUNY that fall, he was ready to test his theory. He filled two tiny tubes with “light” water and an outer tube with “heavy” water, distinguishable by their different molecular structures (heavy water contains an isotope of hydrogen with one extra neutron particle). Using his magnetic field gradient technique, he produced a cross-sectional image of the assembly of tubes.

The results were a major breakthrough, but Lauterbur took it in stride. “I knew what I would see by that time,” he says. “It was not a matter of saying ‘Eureka! There’s an image.’ It was more like, ‘Well, I must have done things right, because I got what I expected to see.’”

He submitted a paper on his results to Nature, which promptly rejected it. “Anything new is likely to meet a certain amount of incomprehension at first,” he says. “Many said it couldn’t be done, even when I was doing it.”

Lauterbur knew he had accomplished something with profound implications. The body consists of two-thirds water and is, essentially, a system of water-filled tubes and containersthat is, arteries and organs. His technique enabled researchers to take the scrambled jumble of information coming simultaneously from the entire magnetic field, to decode it, and to trace the radio signals to their precise positions. This refined information could then be reassembled into a complete image. So, he resubmitted the paper, adding a few paragraphs on his technique’s projected ability to make images inside the human body without surgery. The journal’s editors changed their minds and published the article. It was a good decision. Recently, when the journal issued a book on the 21 most influential papers it had published in the 20th century, Lauterbur’s water experiment was included.

From water experiments, he progressed to imaging a live baby clam, a mouse tail, eggplants, even coconuts. Meanwhile, he was pushing magnet companies to make bigger and bigger magnets, so he could test larger and larger objects. He was also generous with his findings, giving lectures on his work around the world and inviting interested colleagues to his laboratory, which moved to the University of Illinois, where he was recruited in 1985. Others looked for ways to advance his NMR imaging. Sir Peter Mansfield at the University of Nottingham found a way to increase the speed of Lauterbur’s imaging process from hours to minutes. His work also enabled NMR imaging to capture moving or flowing images, like a heart pumping blood.

Today, Lauterbur’s epiphany on the second bite of a hamburger has led to magnetic resonance imaging (MRI), a picture-taking technology that lets physicians see inside the body. (The word “nuclear” was dropped from the imaging name because it scared nonscientists, even though the procedure is safer than, for instance, X-rays.) The first MRI machine for imaging of people was built about 10 years after Lauterbur’s paper was published in Nature. Worldwide, more than 60 million MRI scans are taken each year, enabling physicians to diagnose and monitor a range of conditions, including cancer, multiple sclerosis, and heart disease. MRI also benefits millions of people by painlessly ruling out life-threatening conditions.

Vickers isn’t surprised Lauterbur received a call from Stockholm: “The Nobel Prize was awarded for the innovation of what came to be known as magnetic resonance imagingmaking pictures. It was clearly Paul Lauterbur who came up with that idea.”

On December 10, Lauterbur received the Nobel medal, stepping forward in Stockholm’s concert hall to shake the hand of His Majesty Carl XVI Gustaf, the King of Sweden. More than 1,000 onlookers applauded from the floor and from two tiers of Corinthian-columned balconies overlooking the stage. The presenter said: “Your discoveries of imaging with magnetic resonance have played a seminal role in the development of one of the most useful imaging modalities in medicine today. All indications are that it will be even more important in the future of both medical practice and research and, above all, for the patient.”

Back home now, Nobel madness has subsided. His wife, though, still pokes him sometimes. But it’s only to make sure he knows that the phone call wasn’t a dream. He is, indeed, a Nobel Laureate.

Cindy Gill is a senior editor of Pitt Magazine.

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